臺灣博碩士論文加值系統

由於全球各地的氣喘盛行率逐年持續上升，加上近年奈米科技產品日新月異，尤其以具有抗菌功效的奈米銀應用至為廣泛，因此大量勞工可能在生產過程中吸入空氣中的奈米銀微粒；除了關注奈米銀對一般健康勞工的呼吸毒性外，針對氣喘此易感族群的相關呼吸毒理研究也有其重要性。
　　本研究利用蒸氣冷凝法產生奈米銀微粒，以進行氣喘動物之呼吸暴露實驗。一開始要先建立氣喘動物模式，將BALB/c小鼠分為健康(PBS)和氣喘模式(OVA)兩組，再細分為奈米銀暴露組(NP)和過濾空氣控制組(FA)。因此四組分別表示為PBS/FA (N=5)、PBS/NP (N=6)、OVA/FA (N=5)、OVA/NP (N=5)，暴露時間為6小時/天，連續7天，結束後測量各組呼吸道阻力。最後分析氣喘疾病及肺部發炎指標，以及肺部病理組織切片。
奈米銀暴露組所暴露之奈米微粒平均粒徑為32.78nm，質量濃度為3.34 mg/m3，經過連續7天的暴露後，可觀察到在健康組間，分別在肺泡灌洗液 (BALF)的嗜酸性白血球比率、嗜中性白血球比率及總死亡細胞數三個生理指標中，PBS/NP相比PBS/FA皆有上升趨勢；而在氣喘組間，則在血清的免疫球蛋白E(IgE)(呼吸暴露後)、BALF的介白素13 (IL-13)和總死亡細胞數(total cell)，以及呼吸道阻力(AHR)這些生理指標中，OVA/NP 相比OVA/FA皆有上升趨勢。而且肺部病理組織切片的結果也顯示，無論是健康組還是氣喘組，經過奈米銀暴露後的發炎反應會較強烈。
目前針對氣喘疾病的奈米銀呼吸毒理研究非常缺乏，本研究使用由奈米微粒產生器所產生之奈米銀氣膠進行呼吸暴露，可觀察到奈米銀對健康或氣喘小鼠皆有不良健康效應之趨勢，惟此趨勢在統計上並不顯著，推估是由於此氣喘模式中致敏劑劑量過高所致，建議應下調劑量以適用於奈米呼吸暴露研究；此外，過去亦有研究顯示奈米銀微粒對氣喘小鼠反而有抑制發炎的作用，因此目前奈米銀微粒對於氣喘模式小鼠的健康效應未有一致結論，其毒理影響及作用機轉仍有待更多相關研究。

Nowadays, asthma is one of the most common airway inflammatory disease and its prevalence is high in developed and developing countries. A wide range of silver nanoparticle applications has emerged in consumer products ranging from disinfecting medical devices to water treatment. We are interested in the inhalation toxicity of silver nanoparticles in susceptible allergic asthmatic mice.
In this study, silver nanoparticles were produced in a generation system. The BALB/c mice were divided into normal group (PBS) and asthmatic group (induced by OVA injection). These two groups were further exposed for filtered air (FA) (PBS/FA (N=5)、OVA/FA (N=5)) and silver nanoparticles (NP) (PBS/NP (N=6)、OVA/NP (N=5)) 6 hours a day for one week.
The average size and concentration of NP during exposure was 32.78 nm at 3.34 mg/m3. The inflammation and asthma markers including IgE in serum, IL-13, total protein, total cells, proportion of neutrophils, macrophages and eosinophils in bronchoalveolar lavage fluid (BALF) and AHR (airway hyperresponsiveness) were determined.
The results showed that animals had adverse health effects after exposure to AgNPs (silver nanoparticles). In normal group, percentage of neutrophils, eosinophils and total cells in BALF increased after AgNPs exposure as compared to FA control. In asthma group, IgE, IL-13, AHR and total cells also increased after AgNPs exposure as compared to FA control but it was not statistically significant. These results suggested that asthmatic model needs further modification. Additionally, some previous experiments showed that AgNPs might act as anti-inflammatory agents. Thus，further studies are needed to assess the toxicity of AgNPs in allergic asthma model.

摘要 1
Abstract 3
第一章 前言 5
第二章 背景與重要性 6
2.1　奈米微粒特性與毒性 6
2.2 奈米銀微粒 7
2.2.1 微粒特性 7
2.2.2 流行病學研究 7
2.2.3毒理研究 8
2.3 氣喘 10
2.3.1 氣喘疾病 10
2.3.2 氣喘疾病產生機制 11
2.4奈米產生系統 13
2.5 肺部發炎與傷害指標 15
2.6 研究目的 16
第三章 材料與方法 17
3.1 研究架構及時程 17
3.2 氣喘模式建立 18
3.3呼吸暴露 18
3.3.1　奈米微粒特性檢驗 19
3.4 呼吸道阻力測試 20
3.5 肺泡灌洗液 21
3.5.1肺泡灌洗液中總死亡細胞數 22
3.5.2肺泡灌洗液中血球分類計數 22
3.5.3肺泡灌洗液中細胞因子IL-13 23
3.5.4肺泡灌洗液中總蛋白數 24
3.6血液中的IgE 抗體濃度 24
3.7組織病理切片 25
3.8 統計分析 26
第四章 結果 27
4.1微粒產生暴露系統 27
4.2奈米微粒成分分析 27
4.3 氣喘疾病生理指標 28
4.4 呼吸道阻力 29
4.5 肺部發炎指標 29
4.6組織病理切片 30
第五章 討論與建議 31
5.1 奈米微粒產生及暴露系統 31
5.2 氣喘疾病及肺部發炎指標 34
5.2.1 奈米銀微粒對健康小鼠之呼吸毒理作用 34
5.2.2奈米銀微粒對氣喘小鼠之呼吸毒理作用 35
5.3 組織病理切片 37
5.4肺泡灌洗液中總死亡細胞數及血球分類之計數 37
5.5結論及建議 38
第六章 參考文獻 39

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